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基因编码的氧化还原传感器。

Genetically encoded redox sensors.

作者信息

Chiu Wai Kan, Towheed Atif, Palladino Michael J

机构信息

Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

出版信息

Methods Enzymol. 2014;542:263-87. doi: 10.1016/B978-0-12-416618-9.00014-5.

Abstract

Endogenous redox sensors detect fluctuations in the intracellular redox equilibrium and are critical for the maintenance of homeostasis. Such systems have been exploited to engineer genetically encoded redox sensors to detect dynamic oxidative changes within a cellular environment. Most genetically encoded redox sensors detect reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide and hydroxyl radical. Technical hurdles including the limited temporal and spatial resolution as well as tissue heterogeneity have complicated the realization of the full potential of genetically encoded redox sensors in animals until recently. Alterations in the concentration and subcellular localization of ROS are integral to numerous disorders, including neurodegenerative diseases and cancer. Thus, genetically encoded redox sensors are useful for the study of the pathogenesis and progression of multiple diseases. Moreover, the ultimate generation of genetically encoded redox sensors provides substantial advantages over conventional methods such as ROS-sensitive fluorescent probes. Here, we review examples of genetically encoded redox sensors, present their application to various fields of biomedical investigation, including the study of oncometabolism, discuss their drawbacks and explore future developments.

摘要

内源性氧化还原传感器可检测细胞内氧化还原平衡的波动,对维持体内稳态至关重要。此类系统已被用于设计基因编码的氧化还原传感器,以检测细胞环境中的动态氧化变化。大多数基因编码的氧化还原传感器可检测活性氧(ROS),如超氧阴离子、过氧化氢和羟基自由基。直到最近,包括有限的时间和空间分辨率以及组织异质性在内的技术障碍,使得基因编码的氧化还原传感器在动物体内充分发挥其潜力变得复杂。ROS浓度和亚细胞定位的改变是许多疾病(包括神经退行性疾病和癌症)不可或缺的一部分。因此,基因编码的氧化还原传感器对于研究多种疾病的发病机制和进展很有用。此外,基因编码氧化还原传感器的最终产生比诸如对ROS敏感的荧光探针等传统方法具有显著优势。在此,我们回顾基因编码氧化还原传感器的实例,介绍它们在生物医学研究各个领域(包括肿瘤代谢研究)中的应用,讨论其缺点并探索未来发展。

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